Another key element of the study is the analysis of predictive biomarkers, which will be performed in serum and tumor tissue, respectively. Serum samples will be collected at prespecified timepoints throughout the study and analysed by SELDI-TOF-MS and DIGE. Candidate proteins are thought to predict therapeutic outcome and candidates are subject for target validation by Western Blot or ELISA. In addition, formalin-fixed paraffin-embedded (FFPE) tumor tissue will be collected prospectively and analysed for micro RNA (miRNA). Candidate miRNAs that predict therapeutic outcome will be validated by quantitative RT-PCR. Furthermore, circulating tumor cells (CTCs) will be generated from blood drawings during routine visits. The primary objective is to correlate the marker profile defined from the FFPE tissue with the profile obtained from CTCs in order to validate expression based markers ant their change during different treatment lines.